ALP-1 Continuous Intravenous Infusion to Maintain Clinical Stability in Advanced Heart Failure

May 13, 2023 updated by: Biopeutics Co., Ltd

Phase 3 Study of Alprostadil Continuous Intravenous Infusion to Maintain Clinical Stability in Severe Heart Failure Patients

This is a global multicenter, doubleblind, placebo-controlled, randomized, parallel-group study that compares ALP-1 given in a continuous infusion and placebo in patients with advanced HF. The difference between the two groups for the primary endpoint will be compared after 6 months of study drug therapy (Double-Blind Treatment Phase).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This multicenter, double-blind, placebo-controlled, randomized, parallel-group trial will study up to approximately 700 patients with advanced HFrEF who are not expected to receive heart transplant or LVAD placement for 6 months after enrollment. Eligible patients will be randomized (1:1) to receive either alprostadil 250 μg/day, regardless of body weight, or placebo (normal saline) given in a continuous infusion. The treatments are further described in the section on Dose/Route/Regimen. Study drug administration will continue until study closure so long as clinically tolerated and the mortality endpoint has not been achieved; patients are to be followed for survival regardless of whether or not they remain on study drug. The difference in mortality rates between the two groups will be compared after approximately 350 deaths, LVAD placements, or heart transplantations have occurred. The study will include an embedded pilot evaluation of secondary nonfatal clinical endpoints and AESIs/ tolerability for purposes of possible protocol modification. Specifically, selected data for the first 70 patients entered (i.e., randomized) will be evaluated in an unblinded manner after the 6-month assessment of the last surviving patient (of the first 70 randomized patients) to discern the effects on (1) patient global assessment, KCCQ, and worsening heart failure events; (2) the occurrence of hypotension, joint/bone pain, diarrhea and headache; and (3) difficulties with protocol implementation. The interim assessment and possible revision of the primary endpoint are discussed further below in the roles of the independent review committees and in the Study Power and Planned Sample Size section.

The screening activities will be performed on stable patients on an outpatient basis or on recently hospitalized patients (inpatient) who are otherwise ready for discharge after clinical stabilization and stabilization of dose of diuretics. Selected patients need to be on all appropriate doses of recommended HF therapy as judged by the Investigator. Screening should not exceed 14 days. The following independent committees will be established and operate under charters outlining operational procedures and responsibilities, briefing desccribed as follows:

  • A Steering Committee (SC), involved in initial protocol development, will review selected data from the embedded pilot phase; all-cause mortality data will not be shared. Following the placement of the central catheter in the first 70 patients, a determination will be made whether or not the subsequent entered patients need to be hospitalized for the first 24 hours; this assessment will be on the basis of blinded data accrued until discharge and the initial study nurse home visit. Once the last of the first 70 patients achieves the 6-month milestone, unblinded data, other than mortality, will be reviewed. If the analysis indicates that there is little unblinding based on tolerability (i.e., AESIs) and there is a reasonable expectation of clinical benefit on one or more of the secondary endpoints, the SC may designate one as primary or design and implement a "hierarchical composite" of the nonfatal and fatal events as the primary endpoint to be applied to all patients randomized into the trial AFTER the 70th randomized patient. If this were to occur, all-cause mortality would become a key secondary endpoint, to be analyzed for non-inferiority based on all randomized patients inclusive of the first 70 patients.
  • A Data Safety Monitoring Board (DSMB) will review unblinded mortality and safety data at regular intervals throughout the study. The role of the DSMB will primarily be to advise the Sponsor on whether or not the study should continue.

Study Type

Interventional

Enrollment (Anticipated)

1500

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Vienna, Austria
        • Medical University Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

  1. Patients older than 18 years of age, of any gender/sex and race/ethnicity
  2. Patients with a diagnosis of advanced HFrEF as evidenced by (all must apply):

    1. Left ventricular ejection fraction (LVEF) ≤30% by any acceptable method at the time of screening or documented within the previous 3 months
    2. Nt-proBNP >3000pg/mL or BNP >600pg/mL at screening
    3. New York Heart Association (NYHA) functional class IIIb or IV, i.e., chronic dyspnea or fatigue at rest or with minimal exertion at the time of screening or within the previous 3 months
    4. Renal dysfunction reflected by a glomerular filtration rate (GFR) <60 mL/min approximated by the Modification of Diet in Renal Disease formula.
    5. A clinical summary scoreof KCCQ of <50
    6. Patients on all appropriate recommended HF therapy.
  3. Patient should not be receiving continuous or planned intermittent intravenous infusions with a positive inotropic or vasodilator drug in a non-hospitalized setting
  4. Patients should not be considered as candidates for heart transplantation or LVAD for at least 6 months from randomization according to the opinion of the treating physician.
  5. Women of childbearing potential (i.e., who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months) must commit either to abstain continuously from heterosexual sexual contact or to use at least one "highly effective" method of birth control (e.g., intrauterine device [IUD], hormonal contraception, tubal ligation, or partner's vasectomy) or two "effective" methods (e.g., latex condom, diaphragm, or cervical cap), beginning 4 weeks prior to screening and throughout study participation.

    Note: As alprostadil is not genotoxic and female sexual partners of male study participants are not likely to have substantial exposure via semen, there are no contraception requirements for men.

  6. Patients must be willing and able to give written informed consent, including local data privacy consents, as required

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: trial arm
6 months central continuous infusion with Alp_1 by infusion pump.
central venous access continuous delivery with 500mcg/48 hours in active arm
Placebo Comparator: Placebo arm
6 months central infusion with NS by infusion pump with exact infusion rat as trial arm.
central venous access continuous delivery with 500mcg/48 hours in active arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to all-cause mortality (defined as death, heart transplant, or LVAD placement)
Time Frame: 6 months infusion
To access the effect of continue long term ALP-1infusion at a fixed dose of at 500mcg/48 hr. in patinets with advanced heart failure with reduced ejection fraction(HrEF) compare to placebo.
6 months infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the effect of continuous long-term alprostadil infusion compared to placebo on secondary efficacy endpoints over 6 months ALP-1-infusion over 52 weeks compared to placebo in patients with advanced HFrEF
Time Frame: 6 months

Patient Global Assessment

  • Change from baseline in Kansas City Cardiomyopathy Questionnaire [KCCQ]
  • Worsening heart failure events
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Martin Huelsmann, MD, Medical University Vienna, department of Cardiology
  • Principal Investigator: Noemi Pavo, MD PhD, Medical University Vienna, department of Cardiology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2023

Primary Completion (Anticipated)

November 1, 2024

Study Completion (Anticipated)

December 1, 2026

Study Registration Dates

First Submitted

January 14, 2008

First Submitted That Met QC Criteria

February 6, 2008

First Posted (Estimate)

February 7, 2008

Study Record Updates

Last Update Posted (Actual)

May 16, 2023

Last Update Submitted That Met QC Criteria

May 13, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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